Serum leptin levels in Iranian patients with Parkinson's disease.

Background: Parkinson's disease (PD), the second most prevalent neurodegenerative disorder, has been related with weight loss and energy balance. Some studies showed that leptin might be playing an important role in satiety, energy balance and immune response. The aim of this study was to evaluate serum leptin level in patients with PD and its association with clinical severity. Methods: In this cross-sectional study, 35 patients with PD and 51 healthy controls (HCs), matched for age, sex and body mass index (BMI), were recruited. Serum leptin level was measured and clinical characteristics and demographic data of patients were recorded. Results: The mean age of patients with PD and HCs were 59.80 ± 11.40 and 62.18 ± 11.60 years, respectively. Serum leptin concentration was not statistically different between patients with PD and HCs (21.1 ± 23.1 ng/ml vs 25.9 ± 21.8 ng/ml, P = 0.280). There was no relation between plasma level of leptin and clinical severity of patients with PD. Conclusion: Our findings suggest that serum level of leptin is neither implicated in the pathogenesis of PD, nor decreases as disease progresses.


Introduction
Parkinson's disease (PD) is the most frequent movement disorder that commonly affects elderly people. 1 Initially, PD was known as a motor disorder with principal symptoms of bradykinesia, resting tremor, rigidity and postural instability. 2 In the last decade, several studies have emphasized on impact of non-motor symptoms (NMS) such as depression, constipation, pain and sexual difficulties in progression of disease and patient's quality of life (QOL). [3][4][5][6] Some studies demonstrated that patients with PD have weight loss and reduced body mass index (BMI). 7,8 Nevertheless, the cause of these events is not clear.
Leptin is a long acting endocrine peptide hormone produced by adipose tissue. Moreover, a small amount of leptin secretes from brain. Leptin controls energy balance through suppression of food intake, glucose metabolism and energy expenditure. 9 Leptin crosses the blood-brain barrier (BBB) and stimulates hypothalamic receptor and sympathetic pathway, resulting in controlling energy intake and energy expenditure. 10 Previous studies found leptin serum levels in patients with PD lower than that in healthy controls (HCs), though the correlation of weight loss and leptin levels was not

Iranian Journal of Neurology
http://ijnl.tums.ac.ir 4 April confirmed. 11 Furthermore, previous studies revealed that patients with PD have lower BMI and lower serum concentrations of leptin compared with HCs. Nevertheless, there is not significant association between serum concentrations of leptin and BMI, and this correlation is not clear exactly. 12,13 Animal and human studies demonstrated the regulatory function of leptin in nervous system and showed that non-motor manifestations such as cognitive dysfunction of patients with PD as well as mesostriatal and mesolimbic dopaminergic pathways are affected by serum and cerebrospinal fluid (CSF) level of leptin. [14][15][16][17][18] On the other hand, both motor symptoms and NMS influence the energy intake and energy expenditure.
We preformed the present study to evaluate leptin profile in patients with PD and assess the possible relation between motor symptoms and NMS of patients with serum level of leptin.

Materials and Methods
We enrolled thirty five eligible patients (25 men and 10 women) with idiopathic PD (IPD) who were admitted to Al-Zahra hospital, Isfahan, Iran. Fifty one healthy people (28 men and 23 women), matched for sex and age, were studied as control group. The study was approved by the regional bioethics committee of Isfahan University of Medical Sciences, and written informed consents were obtained from all patients prior to enrollment. All patients were visited by a neurology specialist in movement disorders, and diagnosis of PD was stablished based on United Kingdom Parkinson Disease Society Brain Bank (UK-PDS-BB) criteria. 19 The subjects who were unable to ambulate, patients with systemic diseases including endocrine and malignant diseases, and those with psychiatric disorders (psychosis and severe depression) were excluded. Moreover, patients treated with medications influencing nutritional state and/or BMI such as corticosteroids, antihistamines and antipsychotic at least for six months, were excluded. None of the patients had nausea or anorexia due to dopaminergic medication and their dietary habits did not alter during the study.
Motor symptoms and NMS of patients with PD were assessed using unified Parkinson's disease rating scale (UPDRS) parts I, II, III and IV. Clinical status of the patients was evaluated by Hoehn and Yahr scale (HY scale). Cognitive state of patients was surveyed using Mini Mental State Examination (MMSE). In addition, BMI of patients and HCs were calculated.
A single 3ml venous blood sample was collected from all patients. Serum was separated within 30 minutes and sorted at -80 ∘ C until analysis for leptin. Serum leptin levels were measured by a leptin radioimmunoassay (RIA) (Linco Research Ltd., St. Charles, MO, USA) and all samples were analyzed in duplicates in the same assay.
All statistical calculations were done using SPSS software (version 20, IBM Corporation, Armonk, NY, USA). Data were expressed as means ± standard deviation (SD), median, and frequency. The one-sample Kolmogorov-Smirnov test was performed for checking variables normality. The between group differences and correlation were assessed using independent sample t-test, Mann-Whitney U test, Spearman and Pearson's correlation, respectively. Statistical significance (P value) was set at the level up to 0.05. Table 1 demonstrates demographic features and clinical characteristics in patients with PD and HCs. The one-sample Kolmogorov-Smirnov test showed normality of variables (K-S = 1.354, P = 0.051).  The UPD with leptin P = 0.050) P = 0.023 In agreement with previous studies, gender differences relate to leptin levels. Several studies in recent years have shown that leptin levels are lower in male PD patients in comparison with female ones. There was abundant evidence to prove roles of increased proportion of adipose tissue and increased production of leptin per body fat mass unit in this correlation. 11,28 Moreover, such studies suggest association between androgenicity in individuals with leptin levels that support gender differences in serum leptin level. 29,30 The present results remain in agreement with the majority of published data showing a progressive increase in the leptin serum levels with an increase in BMI in participants. 21,22 In these studies, a leptin level was not different between PD patients and HCs, but leptin level correlated with BMI.

Results
Association of leptin with BMI is reported in healthy population and other disorders including polycystic ovarian disease (PCOD) and rheumatoid arthritis (RA). [31][32][33][34][35] Investigation on patients with PCOS reported that leptin concentration associated with BMI, and was not correlated with hormonal indices in PCOD patients. Moreover, leptin level was different between obese and non-obese women. 32,33 In RA patients without any inflammatory disorders, leptin level correlated with BMI, although its levels were similar between patients and HCs. 34,35 Deep brain stimulation (DBS) in the subthalamic nucleus (STN) caused weight gain in PD patients, but leptin levels did not change after surgery. 36 These findings reinforce the hypotheses that leptin level alterations in some disorders such as PD associates with BMI and fat mass rather than disorder. The results and characteristics of all previous studies that investigated leptin levels in PD patients are summarized in table 2.
A limitation of our study and previous studies was the small sample size. We did not evaluate fat mass of participants, while it can affect circulatory leptin levels and clarify relation of leptin levels with PD.

Conclusion
In the light of all previously stated facts, we can conclude that circulating leptin level in patients with PD is not different from healthy population and is not associated with disease severity, duration of disease, and clinical status.

Conflict of Interests
The authors declare no conflict of interest in this study.